1. Technical Field
The present invention is related generally to vaccines against rotavirus diseases. More particularly, the present invention is related to a method of preparing a vaccine against rotavirus diseases comprising producing a pure inoculum of live rotavirus, attenuated either naturally or through reassortment, said attenuated rotavirus having in the genome thereof the fourth rotaviral gene segment with a nucleotide sequence associated with naturally attenuated human rotaviruses.
2. State of the art
It is generally recognized that there is a need for rotavirus vaccine in both the developed and developing countries. (Kapikian, et al. Rev. Inf. Dis. (1980), 2:459-469). The importance of rotaviruses as a cause of severe diarrhea in developed countries has been highlighted in numerous cross-sectional studies of infants and young children admitted with diarrheal diseases to the hospital. (Kapikian, et al. Rev. Inf. Dis. (1980) 2:459-469). For example, in a period exceeding eight years (January 1974-July 1982) rotaviruses were detected in feces of 34.5% of 1,537 patients admitted with diarrhea to The Childrens Hospital National Medical Center in Washington, D.C., (Brandt, et al. J. Clin Microbiol. (1983), 18:71-78), and in a Japanese study extending between 1974 and 1981, 45% of 1,910 pediatric patients admitted with diarrhea shed rotavirus. It is obvious from these and various other cross-sectional studies in developed countries that rotaviruses are indeed the major known etiologic agents of severe infantile gastroenteritis requiring hospitalization.
U.S. Pat. Nos. 4,624,850; 4,571,381; 4,190,645; 4,341,870; 4,341,763 and 4,205,131 describe a variety of rotavirus vaccines and/or methods of preparing the same. Other rotaviruses such as bovine rotavirus strains NCDV and WC3, and rhesus rotavirus strain MMU 18006 have also been studied. However, a vaccine comprising live attenuated human rotavirus strain which possesses, either naturally or through genetic reassortment technology, a highly conserved fourth viral gene segment, has not heretofore been suggested or employed as means for inducing immunity against rotavirus diseases without producing unacceptable pathological side effects in the susceptible host.